A blood clot within an artery is known as an arterial thrombosis. Arterial thrombosis is responsible for heart attacks, strokes and peripheral vascular disease (thrombosis in leg arteries). Heart attacks and strokes are a major cause of death and serious illness. In the UK, 25 per cent of male deaths are due to a heart attack, while about 12 per cent of deaths are due to a stroke. Strokes are also the major cause of disability in the Western world.
Arterial thrombosis is primarily platelet-mediated, either due to increased shear or exposed collagen.
Anticoagulatants may be used for control of cardiovascular disease [16]. However there are two major problems with heparins and coumarin derivatives (like warfarin) which are that they cause bleeding and are most effective in fibrin-rich thrombosis, such as that seen in venous thrombosis and arterial fibrillation, but not in platelet-rich (arterial) thrombosis.
The same limitations affect pure thrombin inhibitors like ximelagatran [17].
In order to obtain favourable modification of platelet-induced arterial thrombosis in atherosclerotic disease (increasingly being called atherothrombosis), antiplatelet agents are used. The reversal of platelet activation in atherosclerosis has been shown to have a favorable outcome [2].
Aspirin has been the most widely used agent; it blocks the thromboxane pathway effectively. However due to certain limitations with aspirin, a newer drug, clopidogrel, is currently preferred. This antagonises the P2Y12-receptor. Present therapies such as those discussed above may cause bleeding by interference with COX1, the P2Y12 receptor or the platelet fibrinogen receptor complex, all of which can be associated with bleeding complications. There is also resistance in the population to certain of these therapies [139].
Thus it can be seen that methods and materials which could modulate platelet-induced arterial thrombosis without significant bleeding complications would represent a contribution to the art.
It has been claimed that blockade of the (P13K)p110β isoform of the GPIIb/IIIa adhesion bonds eliminates occlusive thrombus formation without prolonging bleeding time [152].
The use of the antiplatelet drug target in atherosclerotic diseases is discussed by Belcher, Drake-Holland, and Noble in Volume 6, Number 1, March 2006, pp. 43-55(13) (Bentham Science Publishers). The document is a general review of antiplatelet therapy based on the mechanisms of platelet rich arterial thrombosis.